ABSTRACT
Purpose
To investigate the influences of stability of doxorubicin (DOX) retained in PEG-PE/HSPC micelles on its biodistribution, toxicity and anti-tumor activity in mice.
Methods
We incorporated HSPC into PEG-PE micelles at various molar ratios by a self-assembly procedure. Micelles were characterized by dynamic light scattering, transmission electron microscope, atomic force microscopy. Agarose gel electrophoresis assay was used to detect stable retention of DOX in micellar preparations. Biodistribution, toxicity and anti-tumor activity of doxorubicin encapsulated in PEG-PE/HSPC micelles in mice were investigated.
Results
HSPC incorporation not only changed the size and shape of PEG-PE micelles, but also decreased the ability of DOX stable retained in PEG-PE micelles, resulting in a great discrepancy in biodistribution, toxicity and anti-tumor activity among micellar DOX preparations. DOX encapsulated in PEG-PE micelles (M1-DOX), with narrower size distribution and greater stability, demonstrated better cytotoxicity in vitro and low systemic toxicity with superior anti-tumor metastasis activity in vivo.
Conclusions
Encapsulation of DOX into PEG-PE micelles showed the best therapeutic activity and lowest systemic toxicity compared to other HSPC-incorporated PEG-PE micellar preparations. Stable retention of drugs within micelles is important and is determined by compatibility between drugs and polymer blocks.
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ACKNOWLEDGMENTS & DISCLOSURES
This work was supported by grants from State Key Development Plan Project (2007CB935801), the National Nature Sciences Foundation of China (30901869).
Dr Junfeng Hao of the IBP core facilities centre was gratefully thanked for her help for Histopathology and TUNEL assay.
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Xiuli Wei and Yiguang Wang contributed equally to this work.
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Wei, X., Wang, Y., Zeng, W. et al. Stability Influences the Biodistribution, Toxicity, and Anti-tumor Activity of Doxorubicin Encapsulated in PEG-PE Micelles in Mice. Pharm Res 29, 1977–1989 (2012). https://doi.org/10.1007/s11095-012-0725-5
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DOI: https://doi.org/10.1007/s11095-012-0725-5